Bladder Anatomy and the Latest Bladder Cancer Research Studies

Following its exit from the kidneys though the ureters, urine enters the bladder, a muscular organ that collects and expels urine through the urethra. The bladder epithelium, or urothelium, is a transitional epithelium that is highly elastic to accommodate for expansion and contraction.

Smooth muscle cells comprise the muscular wall of the bladder, also called the detrusor muscle. This muscle is responsible for the contractile function of the bladder, relaxing while the bladder fills, and contracting to expel urine through the urethra once the bladder is full.

Bladder cancer encompasses both non-muscle-invasive bladder cancer and the more advanced muscle-invasive cancer, which often metastasizes. Patients with non-muscle-invasive bladder cancer often have a favorable prognosis, but patients with muscle-invasive cancer, once metastasis occurs, have poor survival outcomes.

Research Studies Featuring Lifeline® Bladder Cells

Single-agent treatment of bladder cancer can lead to toxicity and/or resistance. Islam et al. set out to determine whether combined treatment of bladder cancer cells with acetazolamide (AZ), a carbonic anhydrase inhibitor, and sulforaphane (SFN), an isothiocyanate molecule, could lead to more robust anti-tumor activity than either single agent. They found that combined therapy had multiple anti-tumor effects and was more potent than either drug alone. The anti-tumor effects of combination therapy included: decreased bladder cancer cell viability, decreased proliferation, decreased clonogenic potential, decreased bladder cancer cell xenograft tumor growth,  and increased apoptosis.

The researchers demonstrated that these effects were likely mediated through inhibition of the PI3K/Akt signaling pathway by combination therapy. Additionally, combined AZ and SFN treatment resulted in decreased E-cadherin, N-cadherin, and vimentin, suggesting that combination therapy may alter epithelial and mesenchymal characteristics. The authors used Lifeline® normal bladder uroepithelial cells to show that AZ and SFN treatment also affected viability and proliferation of normal, non-cancerous cells. Together, their results suggest that combined AZ and SFN therapy has more potent anti-tumor activity than either drug alone.

The mitochondrial H⁺-ATP synthase synthesizes ATP during oxidative phosphorylation and its function is critical for apoptosis.  ATPase inhibitory factor 1 (IF1) inhibits the H⁺-ATP synthase, and upregulation of IF1 by cancer cells is a mechanism by which cancer cells may be come resistant to apoptosis. Wei et al. established that IF1 is overexpressed in bladder cancer and IF1 knockdown in bladder cancer cells causes decreased proliferation and migration. In particular, the authors found that IF1 knockdown arrests cells at the G0/G1 cell cycle stage, suggesting that IF1 regulates cell cycle entry at this stage. Their study suggests that IF1 overexpression in bladder cancer may facilitate cell proliferation and migration, making IF1 a potential therapeutic target of interest.

Lifeline® offers bladder cells from multiple bladder origins including:

• Bladder dome epithelial cells, optimized for growth in UroLife™ D Medium
• Bladder apex epithelial cells, optimized for growth in UroLife™ A Medium
• Normal bladder fibroblasts, optimized for growth in FibroLife® Medium
• Normal bladder smooth muscle cells, optimized for growth in VascuLife® SMC Medium

Have you used Lifeline® cells in your research? Share your studies with us and your research could be featured here on our blog!